RECOMMENDED CANCER, STARVING DIET, MACROPHAGES


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3-bromopyruvate, starving cancer
90% CHEMO SUCKS--BMJ REVIEW, 2016
pharma and chemo--sucks
Cancer basics and starving cancer--jk
Starving cancer by fasting and ketogenic diet, a review
Cancer as a metabolic disease, starving cancer--Seyfried, 2014
Highlites of Seyfried 2014 Plus 2 more articles
Warburg effect--Dr. Fung Blog-2-18
Vitamin C prolongs life metastatic patients
Ketogenic diet starves cancer, Seyfried Journal 2007
Role of Macrophages in metastatic cancer
Metabolic pathways and cancer growth--2008 review
Glutimate cancer treatments
Glutamine and cancer-2001 review
Blocking Glutimate metabolism by cancer
Ketogenic diet starves cancer, known as Warburg effect, 1924
Otto Warburg's article plus study of Warburg effect
Mega Vitamin C slows cancer invasion, Pauling trial
3-bromopyruvate, starving cancer

No entry for fasting or keto

Ganapathy-Kanniappan, Shanmugasundaram, Rani Kunijithapatham, (of John Hopkins University School of Medicine) et al, Jan 2013 Anitcancer efficacy of metabolic blocker 3-bromopyruvate:  specific molecular targeting

Anticancer Efficacy of the Metabolic Blocker 3-Bromopyruvate: Specific Molecular Targeting

Abstract

The anticancer efficacy of the pyruvate analog 3-bromopyruvate has been demonstrated in multiple tumor models. The chief principle underlying the antitumor effects of 3-bromopyruvate is its ability to effectively target the energy metabolism of cancer cells. Biochemically, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as the primary target of 3-bromopyruvate. Its inhibition results in the depletion of intracellular ATP, causing cell death. Several reports have also demonstrated that in addition to GAPDH inhibition, the induction of cellular stress also contributes to 3-bromopyruvate treatment-dependent apoptosis. Furthermore, recent evidence shows that 3-bromopyruvate is taken up selectively by tumor cells via the monocarboxylate transporters (MCTs) that are frequently overexpressed in cancer cells (for the export of lactate produced during aerobic glycolysis). The preferential uptake of 3-bromopyruvate via MCTs facilitates selective targeting of tumor cells while leaving healthy and non-malignant tissue untouched. Taken together, the specificity of molecular (GAPDH) targeting and selective uptake by tumor cells, underscore the potential of 3-bromopyruvate as a potent and promising anticancer agent. In this review, we highlight the mechanistic characteristics of 3-bromopyruvate and discuss its potential for translation into the clinic.

http://ar.iiarjournals.org/content/33/1/13.full

Figure 1.

                                                                                       3-bromopyruvate

 

Piece of the complete article of interest

However, the challenge possibly limiting the usefulness of LDH as a therapeutic target lies in the fact that tumor cells can switch to oxidative phosphorylation (mitochondrial respiration), thereby evading the effect of LDH inhibition. Perhaps the recent developments targeting glutamine metabolism along with glucose metabolism could profoundly affect cancer cells (9, 10) [I think only some of them which depends on the degree of dismantling  of the MTD—Check #s 9 &10].

Chemoresistance and systemic toxicities are two of the several factors that can affect the successful translation of drugs to the clinic. Thus, from a clinical perspective, in order to be successful, a potential drug candidate (inhibitor of a target) must possess key attributes, such as (i) the ability to selectively target tumor cells and (ii) molecular specificity resulting in the direct potent inhibition of the target. One such agent, the pyruvate analog, 3-bromopyruvate fulfills these requirements and has generated significant interest due to its remarkable anticancer effects in various tumor types. During the past decade, since its discovery as an anticancer agent, impressive data have emerged providing tremendous insight into the therapeutic efficacy and mechanistic aspects of 3-bromopyruvate action

This article isn’t interested in keto or fasting just adding one or two more drugs to the cocktail  not one entry for keto or fasting

 

Lis, Pawel, Mariusz Dylag, et al, Molecules 2016 21(12), 1730,  The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate  Full

https://www.mdpi.com/1420-3049/21/12/1730/htm   FULL

The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate

Abstract

:

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.

 

unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation.  [DOUBTS IT IS 40% THEN FASTING KETO WOULD ALWAYS FAIL]   Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development. 

 

high glycolysis even in the presence of oxygen, may provide up to 60% of the ATP with the remaining (~40%) being derived from mitochondrial oxidative phosphorylation [5]  As stated above, it should be appreciated that the “Warburg effect” allows cancerous tumors and the viscous cells that comprise them to adapt to hypoxic conditions which frequently develop during their growth [6]. Although uncommon, there are exceptions as some gliomas, hepatomas, and breast cancer cell lines are more dependent on mitochondrial oxidative phosphorylation for their energy source, i.e., ATP [7]. This can be explained by the presence of various bioenergetic phenotypes from the exclusively glycolytic to highly oxidative phosphorylation [8].  Apart from the “Warburg effect”, some cancers also exhibit a phenomenon of the so called “Crabtree effect”. It is short-term and reversible (unlike the “Warburg effect”) and involves the suppression of respiration and oxidative phosphorylation by a high concentration of glucose [11,12]. Moreover, it has been shown many times that cancer cells can reversibly regulate their energy metabolism. This phenomenon observed in vitro must exist also in vivo. With respect to the tumor architecture, the metabolic symbiosis may be considered as a niche where a hypoxic central part utilizes glucose while an edge of the tumor which is better vascularized uses lactate as a substrate [16]. Therefore, some of the cancer cells within a tumor may have a different phenotype than the other cells [17]. Thus, the ability of cancer cells to undergo short-term and reversible changes in their metabolism may also allow them to avoid the toxic effect of a drug. This is possible as it has been shown in experiments performed in vitro [18,19]. . .  but also amino acids, mostly glutamine, which in addition to serving as an energy source [21] is also a source of amine groups essential for many biosynthetic events, e.g., production of purines and pyrimidines [22]. In addition, cancer cells may utilize metabolic pathways that are highly energy producing, e.g., the mitochondrial beta-oxidation of fatty acids [23]. Finally, it is important to note that the products and intermediates of glycolysis and glutaminolysis are used in the synthesis of many of the molecules needed for intense proliferation [20]..  .2-DG, citrate, and 3-bromopyruvate (3BP) have all been tested recently as potential anticancer drugs acting either via glycolysis inhibition (2-DG and citrate) or glycolysis plus mitochondrial inhibition (3BP). It was shown in vitro that 7-days therapy with 5 mM 2-DG resulted in a strong but incomplete inhibition of growth (60% to over 90%) in 12 different cancer cell lines [51]. A dramatic 100% mortality was shown in the MSTO-211H lung mesothelioma cell line after treating first for 3 days with 10 mM citrate, a physiological inhibitor of PFK1 [52,53], and then with a low dose of cisplatin [54].{but they didn’t try them with keto and fasting]

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As required by law, I am not recommending that the public do as I do.  I am only setting out why some scientist subscribe to a different theory of cancer and its treatment, and what I would do based on their theory.  See your physician for medical advice.